Oligomer-Targeting Drug Development Programs

We are dedicated to developing novel disease-modifying treatments that target the toxic amyloid-β oligomers specifically. Alzinova’s lead candidate, ALZ-101, is in late preclinical development, and ALZ-201 is in early preclinical development. The portfolio is generated from the proprietary AβCC Peptide™ Technology.

ALZ-101

ALZ-101 is a vaccine that stimulates the production of antibodies against the toxic Aβ oligomers. It has completed the preclinical phase. A first-in-human study in patients with mild Alzheimer’s disease will start during the second quarter of 2021.

Preclinical development

Several clinical setbacks within anti-amyloid methods to treat Alzheimer’s disease have highlighted that non-clinical in vivo efficacy studies in transgenic disease models alone cannot prove a drug’s potential. Alzinova has therefore complemented the early selection process with in vitro and ex vivo pharmacology studies utilizing patient-derived toxic material.

In brief, the selection of ALZ-101 was based on three important criteria:

  1. Specificity for the CNS-specific oligomeric forms has been demonstrated in vitro.
  2. Information of potential efficacy has been obtained by assessing the direct toxic effect(s) of brain material, and neutralizing this effect ex vivo.
  3. Target engagement in the CNS has been demonstrated in vivo using a preclinical efficacy model (transgenic mice) which focused on relevant markers of oligomer-pathology.

This combined information serve as a good indicator of ALZ-101’s potential efficacy.

ALZ-101 has also proven to be immunogenic. It generates an immune response that is not associated with any findings suggestive of systemic toxicity in mice, rabbits and non-human primates. A GLP-compliant toxicology and safety pharmacology study in non-human primates demonstrated that it was clinically well tolerated in this species.

Clinical development

Alzinova has designed a first-in-human clinical study to evaluate the safety and immunogenicity of ALZ-101. Exploratory endpoints are biomarkers in cerebrospinal fluid  (CSF) and serum and preliminary efficacy measured with a package of psychometric tests.

The study is planned to start recruitment during the second quarter of 2021. Please return later for more information and updates.

ALZ-201

ALZ-201 is a monoclonal antibody that is specific for the toxic Aβ oligomers. ALZ 201 is currently in preclinical development.

Preclinical development

ALZ-201 was developed using ALZ-101. It is a murine monoclonal antibody of IgG type that is extremely specific for the Aβ42CC oligomers. It completely lacks affinity for monomers, fibrils and all forms of Aβ40. It does not bind the plaques of humans.

Immuodepletion of brain extracts demonstrates that the native Aβ targeted by this antibody is not detectable using Western blots. Despite this, it has a profound effect on the toxicity of the brain extracts, indicating that the amounts of toxic Aβ42 in patient brains are very low.

ALZ-201 is thus a novel antibody with a specificity that differs from known antibodies, and further substantiates that there are oligomer-specific epitopes in full-length Aβ42 that can be targeted with very high specificity without also targeting monomers and fibrils.

Learn more

Learn more about the oligomer target in Alzheimer’s disease, our programs and the potential of our unique proprietary AβCC technology.